CDH1: Options for Managing Cancer Risk

Hereditary diffuse gastric cancer

Hereditary diffuse gastric cancer (HDGC) is an aggressive type of cancer that can be hard to detect, as these cancers spread through the lining of the stomach rather than forming a mass. These cancers may also be referred to as "signet ring cell cancers" because of the way the cells look under a microscope. 

Gastric cancer screening and prevention options

There are two main options for managing HDGC risk in people with CDH1 mutations. 

Preventive gastrectomy

• Preventive gastrectomy (also known as prophylactic or risk-reducing gastrectomy) involves surgery to remove the entire stomach before cancer can develop. The procedure is effective at lowering risk for stomach cancer, but can have a large impact on lifestyle, (such as eating habits, symptoms that happen with eating, and the ability to maintain your weight). It can also have an impact on overall health, (such as increased risk of vitamin and mineral deficiencies, increased risk of bone disease and other effects).

Upper endoscopy and random gastric biopsy

• The goal of upper endoscopy (also called esophagogastroduodenoscopy or EGD) with both gastric biopsies is to try to find evidence of diffuse gastric cancer at its earliest and most curable stage. This screening is done under anesthesia. The endoscopist passes a scope with a video camera through the mouth into the stomach in order to get a close look. The endoscopist then passes a tiny instrument through the scope to take tissue samples from different spots within the stomach. These samples are sent to a pathologist to check them for cancer.
• Experts do not all agree on how well this screening works for finding HDGC in its earliest and most treatable stage.

Expert guidelines

Research has shown that nearly all people with a CDH1 mutation have an early stage of signet ring cell cancer  changes in the stomach (stage 1A), but many will never develop advanced gastric cancer (stage 1b or higher) during their lifetime. Because each person’s risk is different, guidelines recommend that decisions about screening and prevention be based on personal cancer history, family history and discussion with an experienced healthcare team. 

Gastrectomy is recommended for people with any of the following:

• a diagnosis of gastric cancer that is stage 1b or higher.
• persistent signs and symptoms that may be associated with a higher stage of gastric cancer diagnosis not explaied by other medical conditions, including: weight loss, feeling full without eating a meal, anemia and abdominal pain.  

• certain findings on EGD that indicate an increased risk for higher-stage cancer. 

For people who do not have any of the findings listed above, you should have a conversation with your healthcare team to decide which risk-management option is right for you. 

This discussion should include the following:

• input from specialists with experience managing CDH1-related cancer risk.
• your personal preferences.
• your medical history.
• your family medical history.  

• the best age to begin surveillance, including whether surveillance should start before age 18 if personal or family history suggests a higher risk.  

If the decision is made to continue surveillance with EGD and biopsy:

• the procedure should be repeated every 6-12 months. 
• all people undergoing EGD should be tested for the bacteria, H. pylori and treated if positive.  

Breast cancer risk management guidelines

Below are the expert guidelines for breast cancer risk management. 

Other cancer screening and prevention

There isn’t enough research to show that people with a CDH1 mutation benefit from extra screening or prevention for other types of cancer. Because of this, experts recommend following general population screening guidelines and considering your family history when managing these risks. National guidelines exist for screening the following cancers:

• cervical
• colorectal
• lung
• prostate